Ortho and meta substitution

The influence of steric effects on the photocyclization process is clearly discernible for the ortho and meta substituted stilbenes. In these cases steric repulsion intervenes as the two C atoms forming the new bond approach. This steric repulsion opposes the stabilizing interactions which promote the cyclization process. As a result the reactivity is decreased. Other consequences of such superimposed steric... 

Intersystem crossing rate constants of ortho- and meta-substituted singlet phenylni-trenes are presented in Table 1Mono- and di-o-fluorine substituents have no influence on ISC rate constants.No effect with meta, meta-difluoro substitution is observed either. Pentafluoro substitution has no effect on fcisc in pentane although a modest acceleration is observed in the more polar solvent methylene chloride.i° - i... 

TABLE 11.3. Intersystem Crossing Rate Constants of Ortho and Meta Substituted Phenylnitrenes"... 

The total phenolic compounds in an aqueous sample can be determined by a colorimetric method using 4-aminoantipyrine. This reagent reacts with phenolic compounds at pH 8 in the presence of potassium ferricyanide to form a colored antipyrine dye, the absorbance of which is measured at 500 nm. The antipyrine dye may also be extracted from the aqueous solution by chloroform. The absorbance of the chloroform extract is measured at 460 nm. The sample may be distilled before analysis for the removal of interfering nonvolatile compounds. The above colorimetric method determines only ortho- and meta-substituted phenols and not all phenols. When the pH is properly adjusted, certain para-substituted phenols, which include methoxyl-, halogen-, carboxyl-, and sulfonic acid substituents, may be analyzed too. 

This pK a is higher than would be anticipated for ortho- and meta- substituted phenols since the o meth-oxyphenol has a pK a of 9.98, m-methoxyphenol a pK a of 9.65 and resorcinol a pK a of F.81 (13). A molecular model of the drug shows that the free rotation of the phenolic hydrogen is hindered by the A -hydrogen and can explain a9-tetrahydrocannabinol s higher pK a. Of course, if solvated dimers, trimers, etc., exist with hydrophobic bonding, the observed pK a could be a hybrid pK a for a solution of such polymers. 

These product ratios show that the orientation of substitution is not random. If each C—H position were equally reactive, there would be equal amounts of ortho and meta substitution and half as much para substitution 40% ortho, 40% meta, and 20% para. This is the statistical prediction based on the two ortho positions, two meta positions, and just one para position available for substitution. 

Activation of aromatic compounds by transition-metal complexes was initially studied with Cr(CO)3 complexes. Nucleophilic addition of 2-lithio-l,3-dithianes to arene-chromium(O) complexes 185 followed usually by iodine-promoted decomplexation affords the corresponding 2-arylated 1,3-dithianes 186. The reaction of //-(toluene)- and (anisole)tricarbonylchromium (185) with compound 161 gave mixtures (52 46 and 10 90, respectively) of ortho and meta substituted derivatives (186) (Scheme 54)244. The meta directing effect was also observed (mainly better than 95%) with amino and fluoro substituted complexes245. 

Ortho and Meta substitution The shift effects are additive. 

In contrast to the lack of selectivity observed in the TS-1 catalyzed oxidation of 3-penten-2-ol (1) (Eqn. 21.5), the oxidation of 1 with tert-butyl hydroperoxide (TBHP) over Cr-PILC gave the unsaturated ketone, 3, in 82% yield (Eqn. 21.13)42 while the oxidation of 1 over a vanadium pillared montmorillonite (V-PILC) gave the epoxy alcohol, 2, in 94% yield.43 V-PILC, however, does promote the oxidation of primary benzyl alcohols to the acids with tert-butyl hydroperoxide. This reaction exhibits shape selectivity in that para-substituted benzyl alcohols are oxidized while the ortho- and meta- substituted species are essentially inert (Eqn. 21.14).44... 

The substitution of the CH group by the CX one (X = F, Cl, Br, I) in phenol is expected to be felt by the aromatic ring as a rather weak perturbation which would enhance the electron donation and modify the electrophilic substitutional indices according to the additive law . As we have shown in Subsections UFA and III.B, in the ortho and meta substituted phenols the orientation of the OH bond in the molecular plane permits the existence of two conformers (Figures 12 and 13). 

A series of aromatic imines are applicable to the present substitution reactions (Scheme 3.8). para Substituted aromatics showed excellent enantioselectivities irre spective of their electronic properties. Ortho and meta substitutions as well as fused ring systems were also applicable. Thus obtained p amino a diazoester products could be transformed into common synthetic intermediates, that is, p amino add derivatives, via simple reduction or oxidation of the diazo moiety. 

The most straightforward cause of shape selectivity is the discrimination between molecules on the basis of their diffusion rates through the channels or cage windows. Microporous solids act as true molecular sieves, because the well-defined pores are able to select molecules on the basis of differences in dimensions of 0.1 A or less. Examples of strong molecular sieving effects include the selection of normal alkanes over branched ones by small-pore solids and the selection of para-substituted over ortho- and meta-substituted aromatics over medium-pore zeolites. This type of selectivity according to molecular diffusion rate may act on both reactant and product molecules. The much faster dehydration of n-butanol compared to isobutanol over Ca-A demonstrated by Frilette and Weisz is the classic example of reactant diffusion... 

Dehydrative condensation of benzofurazan oxide with phenolic enolates affords phenazine di-N-oxides (Scheme 7). The condensation proceeds under mild conditions (NaOH/H20, H2O, MeOH/RNH2, Si02/CHs-CN at room temperature) and can be applied to a broad range of substituted nucleophiles of varying oxidation levels (phenolates, resorcinolates, hydro-quinones, and benzoquinones). A few limitations have been encountered for the phenol, and these include insufficient reactivity of dioxalane-protected p-formyl phenol and decarboxylation of free carboxylates at even mild reaction conditions (NaOH/H20, 60 Nucleophilic attack on the benzofurazan will occur from the para position in ortho- and meta-substituted phenolates, whereas para-substituted phenols will attack from the ortho position. Subsequently, elimination of H2O or ROH will take place if possible otherwise, elimination of H2 will give the phena-... 

PROBLEM 14.33 Use an Energy versus Reaction progress diagram to compare ortho and meta substitution on the trimethylanilinium ion. 

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